Role of Nuclear Receptors in Exercise-Induced Muscle Adaptations

Abstract

Skeletal muscle is not only one of the largest, but also one of the most dynamic organs. For example, plasticity elicited by endurance or resistance exercise entails complex transcriptional programs that are still poorly understood. Various signaling pathways are engaged in the contracting muscle fiber and collectively culminate in the modulation of the activity of numerous transcription factors (TFs) and coregulators. Because exercise confers many benefits for the prevention and treatment of a wide variety of pathologies, pharmacological activation of signaling pathways and TFs is an attractive avenue to elicit therapeutic effects. Members of the nuclear receptor (NR) superfamily are of particular interest owing to the presence of well-defined DNA- and ligand-binding domains. In this review, we summarize the current understanding of the involvement of NRs in muscle biology and exercise adaptation.

Figure 1.

Structure and DNA-binding sites of nuclear receptors (NRs). (A) Schematic representation of the different NR domains. (B) Arrangements of DNA-binding sites of NRs. (X)_n indicates a spacer of n arbitrary nucleotides X between the hexamer half-sites. The repeats are accordingly designated as DR-n, IR-n, or ER-n, for example, DR-1 for a direct repeat with a spacer of one nucleotide.

Figure 2.

Regulation of endurance and resistance exercise adaptations in skeletal muscle by nuclear receptors (NRs) and coregulators. For some NRs, including RORγ, Nur77, Nor1, or AR, a role in both the promotion of an oxidative and a glycolytic muscle phenotype has been proposed in different experimental models.